Open AccessIdentification of transcriptome signature for predicting clinical response to bevacizumab in recurrent glioblastoma
Author(s) -
Choi Seung Won,
Shin Hyemi,
Sa Jason K.,
Cho Hee Jin,
Koo Harim,
Kong DooSik,
Seol Ho Jun,
Nam DoHyun
Publication year - 2018
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1439
Subject(s) - bevacizumab , angiogenesis , biomarker , medicine , transcriptome , oncology , gene signature , gene , angiogenesis inhibitor , vascular endothelial growth factor , vascular endothelial growth factor a , glioblastoma , cancer research , bioinformatics , gene expression , vegf receptors , biology , chemotherapy , genetics
Glioblastomas are among the most fatal brain tumors. Although no effective treatment option is available for recurrent glioblastomas ( GBM s), a subset of patients evidently derived clinical benefit from bevacizumab, a monoclonal antibody against vascular endothelial growth factor. We retrospectively reviewed patients with recurrent GBM who received bevacizumab to identify biomarkers for predicting clinical response to bevacizumab. Following defined criteria, the patients were categorized into two clinical response groups, and their genetic and transcriptomic results were compared. Angiogenesis‐related gene sets were upregulated in both responders and nonresponders, whereas genes for each corresponding angiogenesis pathway were distinct from one another. Two gene sets were made, namely, the nonresponder angiogenesis gene set ( NAG ) and responder angiogenesis gene set ( RAG ), and then implemented in independent GBM cohort to validate our dataset. A similar association between the corresponding gene set and survival was observed. In NAG , COL 4A2 was associated with a poor clinical outcome in bevacizumab‐treated patients. This study demonstrates that angiogenesis‐associated gene sets are composed of distinct subsets with diverse biological roles and they represent different clinical responses to anti‐angiogenic therapy. Enrichment of a distinct angiogenesis pathway may serve as a biomarker to predict patients who will derive a clinical benefit from bevacizumab.